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C Sapienza

Publications and source records attributed to C Sapienza.

At least 55 records · Page 3Linked to original sources
PubMed1992

A reliable method for the use of oligonucleotides as probes in blot-hybridization experiments.

We have developed a ligation and specific-primer radiolabeling method that allows the use of oligonucleotides as probes in blot-hybridization experiments. The major advantage of the protocol is that standard hybridization and washing conditions may be used and yield high signals and low background. The observed increase in the stability and intensity of the hybridization signals appears to result from both increased length and specific radioactivity of the hybridization probe.

Base Sequence↗
PubMed1992

The polar-lethal Ovum mutant gene maps to the distal portion of mouse chromosome 11.

Genome imprinting is the process by which identical alleles at a particular locus may be rendered functionally different depending on the sex of the parent contributing the allele. While several mutations in imprinted genes have been defined, no variants in the regulatory system that gives rise to imprinting have been described. Here we report our genetic analysis of the behavior of the interstrain, polar, embryonic-lethal phenotype known as the "DDK syndrome." We have mapped the interstrain, polar-lethal region of the genome to the distal portion of mouse chromosome 11, near the Xmv-42 locus. We propose that the lethal phenotype is not caused by a standard mutation, but by aberrant imprinting of a gene within this region.

Animals↗
PubMed1992

Genome imprinting and cancer genetics.

Parent-of-origin-dependent modification of the genome (genome imprinting) is thought to be involved in the formation of several types of human cancer. Simple modifications of Knudson's two-hit model give rise to two types of predictions with respect to the genetic behavior of such diseases. In the first, rare alleles of modifier genes will give rise to the retention of the same parent's tumor suppressor alleles in sporadic cases. In the second, other variants of the modifier genes will result in failure to establish linkage between tumor suppressor genes and disease predisposition in familial cases. Both of these predictions are fulfilled by experiment. Additional modifications of existing models are predicted to result in more complex patterns of inheritance. The demonstration of such patterns in human pedigrees will require an extremely sophisticated level of genetic analysis.

Genome, Human↗
PubMed1991

Genome imprinting and carcinogenesis.

The preferential retention of paternal tumor suppressor alleles in sporadic tumors and the failure to demonstrate genetic linkage between disease predisposition and tumor suppressor loci in familial cases indicates that genome imprinting may be involved in the genesis of some pediatric cancers. A genetic model that invokes the activity of modifier loci (imprinting genes) on alleles to be modified (imprinted genes) is able to account for these data. Genome imprinting may be viewed as a special case of dominance modification, differing from other examples only in that the modification of dominance is dependent on gamete-of-origin. Data from human pediatric tumors, transgenes in the mouse and variegating position-effects in Drosophila, indicate that the net effect of modifier loci is the inactivation of alleles at affected loci. Polymorphism at the level of the modifier loci will result in different degrees of modification between individuals. With respect to tumors, the most important mechanism by which these differences are manifested is cellular mosaicism for the expression of a modified allele. Such characteristics are reminiscent of the behavior of variegating position-effects in Drosophila and the application of this paradigm to human disease phenotypes provides both a mechanism by which differential genome imprinting may be accomplished as well as genetic models that may explain the clinical association of syntenic diseases, the association between tumor progression and specific chromosomal aneuploidy and the unusual inheritance characteristics of many diseases.

Alleles↗
PubMed1990

Sex-linked dosage-sensitive modifiers as imprinting genes.

It is proposed that differential genome imprinting is the result of dosage-sensitive modifier genes located on the sex chromosomes. Parallels between variegating position-effects in Drosophila, the phenotype elicited by transgenes in the mouse and data from several pediatric tumors indicate that the net result of the activity of such modifier genes is often cellular mosaicism in the expression of affected alleles. The mechanism by which inactivation of affected alleles is achieved is proposed to be through the formation of heterochromatic domains. Because the relevant sex-linked modifying loci are dosage sensitive in their activity, differential imprinting will occur even within homogeneous genetic backgrounds. The presence of allelic variants at these loci in non-inbred populations will give rise to variation in the observed expressivity and mode of inheritance of affected traits.

Animals↗
PubMed1989

A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting.

Embryonal rhabdomyosarcomas (malignant pediatric tumors of striated muscle origin) have been shown to arise from cells that are clonally isodisomic for loci on chromosome 11p. We determined the parental origin of alleles in this genomic region in familial and sporadic cases of this disease and found that isodisomic chromosome 11p alleles in each tumor were of paternal origin. We have developed a modification of Knudson's two-hit model from these data that is capable of explaining the preferential allele retention and of resolving the apparent contradiction between such specific and early events in several embryonal tumors and discrepancies in the inheritance of predisposition in some of these diseases.

Alleles↗
PubMed1989

Cellular mosaicism in the methylation and expression of hemizygous loci in the mouse.

Proposed models for the inheritance of locus-specific methylation phenotypes in somatic cells include those in which there is stable inheritance of a methylation pattern such that all cells contain a similarly methylated locus, as well as models in which the inheritance of methylation can be variable. We investigated these possibilities by examining the methylation and expression of hemizygous loci in the mouse. Our results demonstrate that differences in both methylation and expression can exist between apparently identical cells and that such mosaicism is genetically controlled.

Animals↗
PubMed1989

Epigenetic and genetic factors affect transgene methylation imprinting.

In some lines of transgenic mice, the methylation of MspI sites within or adjacent to the transgene locus is affected by the sex of the parent from which the transgene is inherited. These differences are consistent with a role for DNA methylation in genome imprinting. In a previous report, we noted that in one such line, all offspring of females exhibited hypermethylation of the transgene while only some offspring of males carried a hypomethylated transgene. In this report, we provide evidence that this phenomenon is controlled by at least two factors, one of which acts in cis and is dependent on the transgene locus, and one of which acts in trans and is supplied by the maternal genome. We also provide evidence that there are genetic differences between inbred mouse strains in the trans-acting factor.

Animals↗
PubMed1982

High-frequency genomic rearrangements involving archaebacterial repeat sequence elements.

Halobacterium halobium is an obligately halophilic archaebacterium of interest to molecular biologists for many reasons, one of which is the unexplained high frequency (10(-4)-10(-2) mutants per cell plated) at which it yields readily identifiable and unstable mutants. We showed previously that the genome of H. halobium contains many (greater than 50) families of repeated sequences whose members are dispersed on both chromosome and plasmid. Here we report that most if not all of the members of most of these repeat sequence families effect or are affected by spontaneous genomic rearrangements. Quantitative analyses show that such repeat sequence-associated rearrangements (which may be of several kinds) occur at high frequencies (greater than 4 x 10(-3) events per family per cell generation), while unique-sequence DNAs are physically stable. The presence of so many families of elements of such great instability in the halobacterial genome gives it an unusual degree of structural and perhaps functional plasticity.

Genes, Bacterial↗
PubMed1982

Unusual physical organization of the Halobacterium genome.

The genomes of the extremely halophilic bacteria, Halobacterium halobium and Halobacterium volcanii, contain many repeated sequences. These sequences comprise many families, seem to be highly mobile and are arranged in both clustered and dispersed fashions within these genomes. At least some repeated sequences are more strongly conserved between the two species than are unique sequence DNAs.

Biological Evolution↗
PubMed1980

Selfish DNA.

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Animals↗